Bioinert article and its use

Abstract

An article, comprising a substrate and a polymer film attached to the substrate is provided, the polymer film comprising a first layer of a first polymer functionalized by a first functionalization compound covalently bound to said first polymer and bearing at least one catecholic group being present on a surface of the first layer. The polymer film is a layered film, a top layer of which is formed by the first layer, the layered film comprising at least one further layer of at least one further polymer functionalized by a further functionalization compound covalently bound to said further polymer and bearing at least one catecholic group being present on a surface of the at least one further layer, wherein an average ratio of catecholic groups per polymer molecule is equal to or less than 1 in case of the first polymer and greater than 1 in case of the further polymer.

Description

CROSS-REFERENCE TO A RELATED APPLICATION[0001]This application is a National Phase Patent Application of International Patent Application Number PCT / EP2014 / 069091, filed on Sep. 8, 2014, which claims priority of European Patent Application Number 13184328.6, filed on Sep. 13, 2013.BACKGROUND[0002]The invention relates to an article.[0003]An article as described herein has a surface that is modified in order to reduce protein and cell adhesion and can thus be described as antifouling-coated surface.[0004]Biofouling on material surfaces in the biological, medical or diagnostic field is a major problem that can result in inflammation, cell adhesion, irritation of the surrounding tissue, and improper function of devices in vivo and in vitro [1, 1a, 2]. Therefore, improving the bioinert and antifouling ability of material surfaces in contact with biofluids plays an important role, e.g. in medical engineering. Medical implants for example are manufactured from diverse material classes in ...

AI Technical Summary

Benefits of technology

[0086]In another embodiment, the first polymer is additionally functionalized with at least one compound selected from the group consisting of bioactive units or ligands such as amino acids, peptides, monosaccharides, oligosaccharides, polysaccharides, proteins, DNA and RNA. Enzymes and antibodies are further examples of possible bioactive units or ligands. Aptamers are preferred forms of RNA. All of these bioactive units or ligands initiate a specific interaction of certain addressed bio entities with the surface. Thus, by introducing such bioactive units or ligands, specific interactions with, e.g., surrounding tissue, can be enhanced.

[0088]In another embodiment, the first functionalization compound and the further functionalization compound are identical. If also the first bare polymer and the further bare polymer are identical, the first polymer and the further polymer only distinguish each other with respect to the average ratio of catecholic groups per polymer molecule. Such a design of the first polymer and the further polymer allows easy manufacturing of the article.

[0092]The present invention also relates to the use of an article as described hereinbefore as device for in vitro cell culture. For example, the article can be a Petri dish that efficiently prevents growing cells from adhering to the material of the Petri dish.

[0094]In case of a permanent implant, an enhanced version of the article (in which the first polymer is additionally functionalized with at least one compound increasing specific interactions with selected bio entities) is preferred. Such additional functionalization can enhance the ingrowth of a permanent implant into the surrounding tissue.

Problems solved by technology

Biofouling on material surfaces in the biological, medical or diagnostic field is a major problem that can result in inflammation, cell adhesion, irritation of the surrounding tissue, and improper function of devices in vivo and in vitro [1, 1a, 2].

However, most materials exhibit a significant degree of bioincompatibility on the long term leading to serious side effects like improper function of devices, in particular biosensors, rejection of implants, and life threatening restenosis of arterial stents.

Macromolecular tail groups may limit the further adsorption of other feasible adsorbates to form a dense single monolayer due to steric crowding [14].

Unfortunately, despite their comparably easy preparation monolayered coatings often lack stability and easily get destructed.

However, these chemically active adhesive layers show a significant fouling performance most likely due to their charged nature, which is difficult to be completely shielded by grafting bioinert terminal layers on top of it [18,19].

In order to resolve this contradiction between stable coatings on the one hand, and perfectly bioinert surfaces on the other hand, the preparation of stable, highly effective antifouling coatings remains a great challenge, especially when it comes to substrates that are chemically not easy to modify like most polymeric materials.

But it still remains a challenge to immobilize hPG on a broad range of different material surfaces, like titanium dioxide and commodity plastics, by using the same surface linker group.

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